Molecular Pathogens 2024, Vol.15, No.4, 209-218 http://microbescipublisher.com/index.php/mp 215 Moreover, the development of live attenuated vaccines (LAVs) involves the deletion of specific virulence genes, which requires precise genetic manipulation. The safety concerns related to incomplete attenuation or potential reversion to virulence further complicate this process (Gallardo et al., 2018; Liu et al., 2023). Additionally, the identification and validation of viral proteins that can serve as effective vaccine targets are ongoing challenges that require extensive in vivo and in vitro testing (Wu et al., 2021; He et al., 2022). 6.2 Complexity of ASFV-Host interactions The interactions between ASFV and its host are highly complex, involving multiple layers of immune evasion strategies. ASFV has evolved to inhibit both innate and adaptive immune responses, making it a formidable pathogen. For example, ASFV can inhibit IFN production by targeting key signaling pathways such as the cGAS-STING pathway, thereby preventing the activation of antiviral responses (Cheng et al., 2023; Zhu et al., 2023). The virus also modulates the host's inflammatory response by downregulating anti-inflammatory molecules like C1QTNF3, which can lead to uncontrolled inflammation and tissue damage (Lv et al., 2022). ASFV's ability to evade the adaptive immune response is equally sophisticated. The virus can inhibit antigen presentation, induce the production of non-neutralizing antibodies, and prevent apoptosis of infected cells, thereby prolonging its survival within the host (Wu et al., 2021; Wang et al., 2022). These mechanisms not only help the virus evade immune detection but also complicate the development of effective vaccines and therapeutics. Furthermore, the virus's ability to modulate host cell functions at multiple levels, including cytokine production, apoptosis, and autophagy, adds another layer of complexity. For instance, ASFV proteins such as E184L and L83L interact with host proteins to inhibit IFN signaling and promote immune evasion through autophagic degradation of key signaling molecules (Zhu et al., 2023; Cheng et al., 2023). These multifaceted interactions highlight the need for a comprehensive approach to studying ASFV immune evasion, integrating molecular biology, immunology, and virology to develop effective countermeasures against this devastating pathogen. 7 Implications for Vaccine Development 7.1. Understanding immune evasion to design effective vaccines African swine fever virus (ASFV) employs a variety of sophisticated mechanisms to evade the host immune system, which complicates the development of effective vaccines. ASFV targets key immune cells such as monocytes, macrophages, and dendritic cells, inhibiting their ability to produce interferons (IFNs) and other cytokines essential for antiviral responses (Wang et al., 2022 ; He et al., 2022; Yu et al., 2023). The virus also modulates the host's inflammatory response and inhibits apoptosis, further aiding in immune evasion. Understanding these mechanisms is crucial for designing vaccines that can effectively counteract these evasion strategies. Recent studies have identified several ASFV genes involved in immune evasion, such as those regulating NFκB and NFAT pathways, and genes like A238L and A224L that inhibit apoptosis and antigen presentation (Gallardo et al., 2018). These insights are pivotal for developing live attenuated vaccines (LAVs) that can provide robust protection by deleting specific virulence genes (Gallardo et al., 2018; Wang et al., 2022). Additionally, the identification of immune components associated with protection, such as IFNγ-secreting cells and specific antibodies, offers valuable targets for vaccine design (Bosch-Camós et al., 2022). 7.2 Challenges in developing ASFV vaccines Despite significant progress, several challenges remain in developing effective ASFV vaccines. One major hurdle is the complex nature of the virus, which encodes numerous proteins that contribute to immune evasion and virulence (Teklue et al., 2020; Zhu et al., 2022). This complexity makes it difficult to identify the key determinants of immune protection and to design vaccines that can elicit a comprehensive immune response. Another challenge is the limited understanding of the correlates of protection against ASFV. While some live attenuated vaccines have shown promise in providing homologous protection, their efficacy in providing heterologous protection is still under investigation (Sang et al., 2020; Wang et al., 2022). Moreover, the onset and duration of protection induced by these vaccines are often delayed and short-lived compared to vaccines for other diseases (Zhu et al., 2022).
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